A new means of generating tumor-reactive immune cells is not only potentially directly clinically applicable, but it can serve as the source of high-avidity T-cells from which T-cell receptors can be cloned. These selected, cloned T-cell receptors then can be translated into off-the-shelf reagents for adoptive T-cell therapies using new gene engineering techniques pioneered in the intramural CCR/NCI program. Therefore, under an approved CRADA with J &J, the Surgery Branch has embarked on a collaborative project to test the clinical efficacy of autologous lymphocyte cultures generated with this antigen presenting cell line of drosophila origin when given to patients with melanoma in combination with lymphodepletion and low dose IL2. We have entered and treated 3 patients on this experimental protocol and all have come through it well, although no objective tumor responses have been documented yet. In addition, we will be evaluating the avidity of T-cells generated with this technique as compared to other more conventional approaches with the aim of producing TCRs of the highest avidity for use in future gene therapy protocols for patients with melanoma.